1,3-Dipolar Cycloaddition Reaction of d-Glucose-Derived Nitrone with Allyl Alcohol: Synthesis of 2-Hydroxy-1-deoxycastanospermine Analogues

The synthesis and evaluation of glycosidase inhibitory activity of polyhydroxylated indolizidine
alkaloids namely 2-hydroxy-1-deoxycastanospermine 3a,b and 2-hydroxy-1-deoxy-8a-epi-castanospermine 3c,d is reported. The key step involves the intermolecular 1,3-dipolar cycloaddition of
allyl alcohol to d-glucose-derived nitrone 4, followed by tosylation, that afforded four diastereomeric
sugar-substituted isoxazolidines 5a−d with the desired regioselectivity. The one-pot conversion of
5a−d to pyrrolidines 8a−d by hydrogenolysis, removal of 1,2-acetonoide functionality, and
hydrogenation afforded corresponding target molecules 3a−d.

本文报道了多羟基吲哚里西啶生物碱（polyhydroxylated indolizidine alkaloids），即2-羟基-1-脱氧卡斯诺普明（2-hydroxy-1-deoxycastanospermine）3a、b与2-羟基-1-脱氧-8a-表卡斯诺普明（2-hydroxy-1-deoxy-8a-epi-castanospermine）3c、d的合成方法及其糖苷酶抑制活性（glycosidase inhibitory activity）的评价。关键合成步骤为：烯丙醇（allyl alcohol）与D-葡萄糖衍生的硝酮（nitrone）4发生分子间1,3-偶极环加成（1,3-dipolar cycloaddition），随后进行对甲苯磺酰化（tosylation），得到四个具备目标区域选择性的非对映异构糖取代异恶唑烷（isoxazolidines）5a−d。通过氢解（hydrogenolysis）、脱去1,2-丙酮叉保护基并经氢化反应，可将5a−d一锅法转化为吡咯烷类（pyrrolidines）8a−d，最终得到相应目标产物3a−d。